Troubled study at heart of therapy debate

Dr. Rajiv Chandra, standing, with three of his patients that received chelation therapy. (Jacob Langston/Orlando Sentinel)

With $30 million of taxpayer money, researchers set out to conduct one of the largest studies ever of an alternative medical treatment, a controversial therapy for coronary artery disease.

The project was marred with problems from beginning to end.

Because the treatment was so out of step with mainstream medicine, it was difficult to find enough patients to take part.

The researchers failed to inform the subjects that one risk of the treatment was death. In consent form documents, they made a confusing statement about the study drug, implying it was safer than it was.

The researchers overseeing the study stepped up background checks on the doctors involved after some physicians ran into disciplinary problems unrelated to the chelation trial. Two doctors consulting on the trial have been convicted of crimes.

The troubles with the study, called the Trial to Assess Chelation Therapy or TACT, are emblematic of the difficulties faced by the National Center for Complementary and Alternative Medicine as it tries to study alternative treatments in a scientific way.

In its 12 years of existence, NCCAM has found itself funding clinical trials of therapies with weak scientific foundations, from distant prayer as a treatment for AIDS to a risky regimen for pancreatic cancer involving coffee enemas.

The chelation study was one of the center's biggest projects, launched about a decade ago with support from a powerful congressman. Funding came from NCCAM and a second organization within the federal National Institutes of Health, the National Heart, Lung, and Blood Institute.

The project was designed to assess whether intravenous chelation therapy, which helps expel metals from the body, can treat coronary artery disease. Tens of thousands of Americans are choosing to undergo such treatments, even though using chelating drugs as heart medicine originated in decades-old ideas about arterial plaques that have never been proved.

Chelating drugs also carry risks. In fact, the drug being studied, edetate disodium, turned out to be so risky that the U.S. Food and Drug Administration later withdrew its approval. Yet the study was not halted, and the volunteers were not immediately told.

"To subject human subjects to risks for no plausible benefit is really unethical," said Dr. Kimball Atwood, an anesthesiologist at the Newton-Wellesley Hospital in Newton, Mass., and first author of a lengthy critique of the study published in The Medscape Journal of Medicine in 2008.

A co-author of the critique, Liz Woeckner, said the trial is a black eye for the National Institutes of Health.

"(The NIH) is the nation's premier medical research facility. We look up to them. We put our hopes in them. We trust them," said Woeckner, president of Circare, a nonprofit that advocates for people enrolled in clinical trials. "For them to conduct a trial that is unethical and unscientific — and continue to conduct it? It is just mind-boggling."

The Medscape paper also questioned whether the results of the study would be valid, citing flaws that included wrong or incomplete information given to subjects and the tarnished professional records of some researchers.

"The trial's outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose," Atwood wrote in the paper. In an interview, he called the project "rotten to the core."

Dr. Josephine Briggs, head of NCCAM since 2008, declined to discuss the study in detail, saying her center no longer oversees it. She did say such research is difficult to conduct. "It has been hard to complete because of the fact that physicians are highly polarized in what they believe," Briggs said.

She referred questions to the National Heart, Lung, and Blood Institute, which was handed oversight of the trial in 2006. Dr. Susan Shurin, its acting director, said in a written statement that a well-designed, sufficiently large clinical trial was needed because so many people were choosing to receive the therapy.

"The lack of compelling evidence to support a widely practiced therapy is an argument FOR doing a randomized trial, not against it," wrote Shurin, who is board-certified in pediatric hematology-oncology.

TACT's principal investigator, cardiologist Gervasio Lamas, defended the project in a written statement and said researchers are committed to ensuring the highest level of patient safety. Lamas is chairman of medicine at Mount Sinai Medical Center in Miami Beach, Fla.

Lamas emphasized that the study operates under extensive oversight by multiple groups. "We are serious scientists trying to provide needed evidence to define whether chelation therapy for coronary heart disease should be part of the standard clinical armamentarium, or whether the risks of chelation outweigh any possible benefit," he wrote.